USMLE Step 2 CK Sample Questions

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Your First Free Step 2 Sample Question

A  7-month-old girl is brought to the office for follow-up examination 1 week after admission to the hospital because of fatigue and severe anemia. She was admitted for 2 weeks. Laboratory studies on admission showed microcytic anemia and increased concentrations of hemoglobin A2 and hemoglobin F, and the patient received multiple transfusions of packed red blood cells during her hospital stay. Since discharge, she has not had fatigue.

She is breast-fed exclusively and feeds appropriately. Stools are regular. She lives with her parents in a single-family home that was built in 2010. Today, she is alert and playing with her mother. Vital signs are within normal limits. Physical examination shows moist mucous membranes. Cardiopulmonary examination shows no abnormalities. Abdominal examination shows splenomegaly. In addition to chronic transfusions of packed red blood cells, which of the following medications is most likely to improve long-term survival in this patient?

A. Deferoxamine therapy
B. Hydroxyurea therapy
C. Iron supplementation
D. Penicillin prophylaxis
E. Succimer therapy

Answer and Explanation

This patient’s laboratory findings are consistent with β-thalassemia major, and she will be transfusion-dependent throughout her life. She also will require iron chelation therapy with a medication such as deferoxamine or deferasirox to prevent iron overload. 

Hemoglobin A normally is composed of two α chains and two β chains. However, mutations in both β-globin genes result in absent β-globin gene expression, a condition referred to as β-thalassemia major. In these patients, hemoglobin electrophoresis shows increased concentrations of hemoglobin A2 (composed of two α chains and two δ chains) and hemoglobin F (composed of two α chains and two γ chains). 

Newborn patients with β-thalassemia major typically are asymptomatic because hemoglobin F (fetal hemoglobin) predominates during the first few months of life. Affected patients present at approximately 6 to 12 months of age (when hemoglobin A synthesis begins) with fatigue and pallor caused by microcytic anemia. Additional findings can include jaundice and splenomegaly (caused by splenic hemolysis of erythrocytes) and skeletal abnormalities (caused by extramedullary hematopoiesis). Although not mentioned in this question, a peripheral blood smear often shows target cells. 

Patients with β-thalassemia major are transfusion-dependent, meaning that they require chronic packed red blood cell (pRBC) transfusions. However, because each unit of pRBCs contains 200 to 250 mg of iron, chronic transfusion can cause iron overload (secondary hemochromatosis). To prevent this complication, patients also require chelation therapy with one of the following:

• Deferoxamine (give subcutaneously)
• Deferasirox (give orally)

Test-taking strategy: To answer this question correctly, you don’t need to be able to make the diagnosis. The question stem tells you that the patient is transfusion-dependent, which means she is at risk for iron overload and requires iron chelation therapy. Don’t get stuck trying to solve a detail that you don’t need to know.

Did you get it right? The correct answer was A.

Incorrect Answer Explanations

Answer B: Hydroxyurea is given to patients with sickle cell disease (SCD) to increase fetal hemoglobin (HbF) concentrations. Although patients with SCD have increased concentrations of HbF, they typically have near normal concentrations of hemoglobin A2. This patient’s increased hemoglobin A2 suggests β-thalassemia major as the underlying diagnosis.

Answer C: Patients who are transfusion-dependent are at risk for iron overload. Iron supplementation is contraindicated in this patient with β-thalassemia major.

Answer D: Penicillin prophylaxis is recommended to protect against infection from encapsulated organisms postsplenectomy or with diseases associated with functional asplenia (eg, SCD). In patients with β-thalassemia major, splenomegaly occurs as a result of splenic lysis of erythrocytes. This patient’s spleen is functional, so prophylaxis with penicillin is not necessary.

Answer E: Succimer is a lead chelator used in the treatment of lead toxicity, specifically in children. In children, lead toxicity most commonly is the result of living in a home built before 1978. Although often asymptomatic, patients can present with abdominal pain and constipation, cognitive impairment, neuropathy, and encephalopathy. Laboratory evaluation shows microcytic anemia and increased venous lead concentrations. In symptomatic patients and/or those with a lead concentration greater than or equal to 45 ug/dL, treatment involves chelation therapy. Additional lead chelators are listed in the Insight table.

Bottom Line: β-thalassemia major results in microcytic anemia, and hemoglobin electrophoresis shows markedly increased concentrations of hemoglobin A2 and hemoglobin F in affected patients. Because these patients are transfusion-dependent, they are at risk for iron overload (secondary hemochromatosis) and require iron chelation therapy with deferoxamine or deferasirox.

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